The characterization of melatonin receptor subtypes [Mel.sub.1a, Mel.sub.1b, Mel.sub.1c ] (Dubocovich, M. L., Trends Pharmacol. Sci., 16, pp. 50-56 (1995)) in native tissues has been hampered by the lack of selective ligands that can distinguish between them. The affinity of 2-iodomelatonin for melatonin receptor subtypes stably expressed in CHO cells is considerably higher for the human Mel.sub.1a and Xenopus Mel.sub.1c subtypes than for the human Mel.sub.1b subtype. Radioligands with reduced affinity for the Mel.sub.1a and Mel.sub.1c receptor subtypes and selectivity for the Mel.sub.1b subtype are valuable in the characterization of melatonin receptor subtypes. 4-Iodo- and 6-iodomelatonin have the ability to bind competitively with 2-[.sup.125 I]-iodomelatonin at melatonin receptor subtypes. 4-lodomelatonin shows a higher affinity for the Mel.sub.1b than for the Mel.sub.1a or Mel.sub.1c melatonin receptor subtypes. On the other hand, 6-iodomelatonin has similar affinities for the Mel.sub.1a and Mel.sub.1b subtypes but a low affinity for the Mel.sub.1c receptor.
Halomelatonins have been prepared by a number of methods well known in the art. The methodology used to synthesize 4- and 6-halomelatonins is unsuitable for the preparation of radioligands because the halogen is introduced at or near the beginning of the synthesis. Furthermore, because of the high susceptibility of the 2-position of the melatonin for electrophilic attack, direct halogenation of melatonin itself results in predominately 2-halomelatonin.